Functional magnetic resonance imaging (fMRI) is sensitive to hemodynamic fluctuations in the human brain. Functional connectivity maps created by calculating the correlation between fluctuations from different brain areas show high correlation in areas that are known to be strongly connected. The correlation is presumed to be related to coordinated neural activity. This technique is increasingly used to probe networks of brain activity in both normal subjects and patients with neurological disorders. However, the physiological basis of the hemodynamic fluctuations and the connection to underlying neural activity are not well understood. The ultimate goal of our research is to definitively establish the relationship between functional connectivity measured with MRI and neural activity. It is difficult to probe the relationship between the two in humans, and few functional connectivity studies have been performed in animals to date. This study proposes to elucidate the relationship between correlated MRI signal fluctuations and neural activity by combining microelectrode recording and imaging in the rodent. Recording will occur between images, so that electrical coherence and MRI correlations can be directly compared. The specific aim of this proposal is: Determine the relationship between functional connectivity and neural activity by interleaving microelectrode recordings and image acquisition in a rodent model.: Functional connectivity will be measured in rats using perfusion, blood oxygenation, and blood-volume weighted MRI to identify which vascular property is the predominant source of signal fluctuations. Hypercapnia will be induced to determine whether it suppresses connectivity as in human studies. Respiratory and cardiac cycles will be recorded to determine their contributions to correlation. Recording of local field potentials and acquisition of MRI images will be interleaved and acquired as anesthesia level is varied to alter neural activity, and coherence in recordings from each pair of electrodes will be calculated and compared to correlation observed with MRI. The goal of this project is to determine the relationship between functional connectivity and neural activity. This is the first step toward our long-term goal of establishing functional connectivity mapping as a noninvasive tool for the diagnosis and evaluation of clinical neurological disorders. PUBLIC HEALTH RELEVANCE The goal of this project is to determine the relationship between functional connectivity measured with MRI in the rodent and the underlying neural activity. This is the first step toward our long-term goal of establishing functional connectivity mapping as a noninvasive tool for the diagnosis and evaluation of clinical neurological disorders.